Articles/Researches/Clinical Data on Dr. Holly's Drops

[HOSADOS]

hi everyone. I'm looking for any for Articles, Researches and Clinical Data about Dr. Holly's drop (Dwelle, Dakrina, NutraTear and Freshkote).

The aim, is to educate myself and to refer my Ophthalmologists, and if you're interested your Ophthalmologists as well to a "more scientific like" information about those wonderful drops, in order to spread the word and use of this drops for the benefits of many patients. So please post any links or leads to relevant info in addition to http://www.dry-eye-institute.org which most of us are familiar with.

I read that such clinical tests were conducted on Freshkote but couldn't put my hand on any (idealy full articles/researches).

My Ophthalmologist, asked me for this kind of information since he was skeptic about it.

many thanks,

H
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Taken from the first lecture- note that Redkote was renamed and is known as NutraTears:

The properties judged important for efficacy, however, can be found in the eye drops of Aqueous Pharma; Dwelle®, Dakrina®, FRESHKOTE™ and REDKOTE™. The most important parameter, the wetting synergistic polymer combination is found in all four artificial tears. They all also have low viscosity to enhance lid lubrication and decrease shear forces at the vulnerable ocular and tarsal surfaces. The first three of the drops contain high (>50 mmHg) oncotic pressure for healing damaged epithelial tissues. Dakrina® contains vitamin A to improve mucin deficiency, and FRESHKOTE contains lipids for eyes that have lipid abnormality. REDKOTE™ contains vitamin B12 to promote healing of the ocular surface

[liz56]

Hi HOSADOS.

This bit of information is not as comprehensive as the link that you have, but it is a little more from another source:

Taken from The Ocular Surface, April 2007:

4. Osmolarity
Tears of patients with dry eye have a higher tear film osmolarity (crystalloid osmolarity) than do those of normal patients. 28,29 Elevated tear film osmolarity causes morphological and biochemical changes to the corneal and conjunctival epithelium 18,30 and is pro-inflammatory. 31 This knowledge influenced the development of hypo-osmotic artificial tears such as Hypotears ® (230 mOsm/L [Novartis Ophthalmics, East Hanover, NJ]) and subsequently Thera- Tears ® (181 mOsm/L [Advance Vision Research, Woburn, MA]). 32

Colloidal osmolality is another factor that varies in artificial tear formulations. While crystalloid osmolarity is related to the presence of ions, colloidal osmolality is dependent largely on macromolecule content. Colloidal osmolarity, also known as oncotic p ressu re, is involved in the control of water transport in tissues. Differences in colloidal. osmolality affect the net water flow across membranes, and water flow is eliminated by applying hydrostatic pressure to the downside of the water flow. The magnitude of this osmotic pressure is determined by osmolality differences on the two sides of the membrane. Epithelial cells swell due to damage to their cellular membranes or due to a dysfunction in the pumping mechanism. Following the addition of a fluid with a high colloidal osmolality to the damaged cell surface, deturgescence occurs, leading to a return of normal cell physiology. Theoretically, an artificial tear formulation with a high colloidal osmolality may be of value. Holly and Esquivel evaluated many different artificial tear formulations and showed that Hypotears ® (Novartis Ophthalmics, East Hanover, NJ) had the highest colloidal osmolality of all of the formulations tested. 33 Formulations with higher colloidal osmolality have since been marketed (Dwelle ® [Dry Eye Company, Silverdale, WA]).

Protection against the adverse effects of increased osmolarity (osmoprotection) has led to development of OTC drops incorporating compatible solutes (such as glycerin, erythritol, and levocarnitine (Optive ® [Allergan Inc., Irvine, CA]). It is thought that the compatible solutes distribute between the tears and the intracellular fluids to protect against potential cellular damage from hyperosmolar tears.3

[HOSADOS]

reading material from Dr. Holly's website

I highly recommend to anyone interested in the topic or to better understand DES, to review the following lecture / presentation made by Dr. Holly.
The second one is more brief and short, whereas the first one is longer and more detailed-but divided to different topic, so one could easily navigate to the topic that match his interest.

http://www.dry-eye-institute.org/lectures.htm
THE IATROGENIC DRY EYE AND ITS MANAGEMENT
Frank J. Holly, Ph.D., President of the Dry Eye Institute
Based on the Harold Stein Lecture given at the CLES Meeting, in Orlando, FL on 01/23/03. Revised on 03/

Vitamins and Polymers in the Treatment of Ocular Surface Disease
by Frank J. Holly, Ph.D., F.A.A.O
Based on a lecture given before the Annual Meeting of AAO. Published in Contact Lens Spectrum, May, 1990. Reprinted in other journals.
http://www.dry-eye-institute.org/vitapo.html

I highly recommend reviewing the following presentationhttp://http://www.dryeyezone.com/enc...DDE2008-1.html. For me it made this whole issue much more clear and allowed me to 'see' lol and understand the broader picture and context of DES.

What to tell your patients about ophthalmic lubricants" by Frank Holly PhD and Cynthia Brunett BA Presented by Dr. Holly at the International Society of Dakryology and Dry Eye's 2008 Congress in Istanbul, Turkey.
__________________
Rebecca Petris
The Dry Eye Zone

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[HOSADOS]

The main features & properties of Dr. Holly's drops

Here are some quotes from the first lecture/presentation that is related to Dr. Holly's drops.
http://www.dry-eye-institute.org/lectures.htm

EFFICACIOUS ARTIFICIAL TEARS

The following properties/components have found to be important to ensure efficacy:

Achieve complete wetting of hydrophobic surfaces

Elevated oncotic pressure

Nutrients and antioxidants such as
retinoids and cyanocobalamine

AQUEOUS PHARMA EYE DROPS

A: Dwelle®, B: Dakrina®, C: REDKOTE™; D: FRESHKOTE ™

All four have complete wetting ability
Three have high oncotic pressure (except REDKOTE™)
Dakrina also contains vitamin A
REDKOTE™ also contains cyanocobalamine
FRESHKOTE™ also contains lipids

Rational Approach to Post-lasik Dry Eye Management
Eliminate the use of lipid ointment
Eliminate the use hypertonic salt solution
Employ collyrium that contains wetting polymers
(A, B, C, or D)
Employ collyrium w/ high colloidal osmotic pressure (A, B, or D)
Employ collyrium that contains bioavailable vitamin A (B)
Employ collyrium with cyanocobalamine. (C)
Employ collyrium with phospholipids (D)

A=Dwelle, B=Dakrina, C=REDKOTE™, D=FRESHKOTE™


Management of Iatrogenic Dry EyesTreatment Modalities

Supplementation of aqueous tears with
REDKOTE™ (increase BUT, heal surface)
Dwelle (increase BUT, impact eoithelium
Dakrina (increase BUT, improve mucin deficiency)
FRESHKOTE™ (as before plus improve lipid abnromality)

Preservation of aqueous tears with
Goggles, transparent patches
Punctal plugs (start with two)
Avoid ointments and hypertonic preparations

Stimulation of tear secretion with
secretagogues, eledoisin, pilocarpine, cyclosporin

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[HOSADOS]

Dr. Holly on Artificial Tears

here is a quote from the second lecture.
http://www.dry-eye-institute.org/vitapo.html

Artificial Tears

The mainstay of "dry eyes" and, in a broader sense, ocular surface disease, has been traditionally the topical use of artificial tear formulations.3 Generally speaking, such tear substitutes consist of electrolytes at either isotonic or hypotonic levels, water-soluble polymers to increase viscosity, and preservatives if the tear substitute is packaged in multi-dose units. Quite recently, tear substitutes containing nutrients have become commercially available. Some of these preparations also contain polymers for purposes other than that of viscosity enhancement.4

Effect on Tear Film Stability

It has been known for more than two decades that tear film instability in the eye is related to wetting, i.e. the inability of the tears to completely wet the ocular surface.5 Despite this fact, most of the commercial tear substitutes are unable to form a continuous film over a hydrophobic surface.6

Compromised Epithelial Integrity

In ocular surface disease the corneal epithelium often becomes waterlogged (microcystic edema). This condition not only affects its barrier properties but also interferes with its adherence to the underlying basement membrane.7 Hypertonic salt solutions are not effective in remedying this situation as the epithelium becomes quite leaky to electrolytes. On the other hand, high colloidal osmolality, i.e. high oncotic pressure will dehydrate such tissue provided that the magnitude of the pressure is higher than the imbibition pressure of the deturgescent stroma.8

[HOSADOS]

Nutrients In The Treatment Of Ocular Surface Disease

here is a quote from the second lecture.
http://www.dry-eye-institute.org/vitapo.html

NUTRIENTS IN THE TREATMENT OF OCULAR SURFACE DISEASE

Topically Applied Vitamin A

The role and possible efficacy of vitamin A in eye drops have been very much in the news in the last five years and as a result, this topic is quite controversial. It has been shown that normal tears contain certain forms of vitamin A which are solubilized by a protein carrier namely the prealbumin factor.9 It has also been suggested that certain forms of vitamin A, specifically trans-retinoic acid and retinyl palmitate have a healing effect on ocular surface disease especially if squamos metaplasia is present.10 On the other hand, vitamin A used excessively is known to cause dry eye conditions. Such a side effect of Accutane®, an oral medication containing tretinoin and used for the treatment of acne vulgaris is well known.

The positive effect of vitamin C in alkali burns of the eye has been demonstrated by several authors but some questions still remain.11 At least one author suggests that vitamin B6 may also have beneficial effects on the eye.12

Vitamin B12 and the Eye
Vitamin B12-containing eye drop has become commercially available only in the last few months.13 The role of this nutrient is not well know, especially in the eye, so that it should be discussed in more detail (Table I).


Table I.

Role of vitamin B12 in the Eye

Vitamin B12.... Is essential for life and normal cell growth.
Cannot be synthesized by the body.
Increases growth rate of corneal epithelium.
May protect the eye from oxidative free radicals.
Is highly bound by tear proteins.
Is absorbed poorly in the elderly.

Vitamin B12 is an essential product for mammalian life and cannot be synthesized by the body. Its role in pernicious anemia is well known.14 It is less known that this vitamin appears to play an indispensable role in the growth of the epithelial cells especially of the mucous membranes. Hence, vitamin B12 may be considered vital for the maintenance of healthy ocular surface.15,16

Vitamin B12 is a vital co-enzyme in the production of DNA from RNA and is therefore an essential component for normal cell growth and division.17 This vitamin also helps to maintain one of the body's vital antioxidant systems, i.e. glutathione. This system protects cells from damaging oxidative free radicals.18 Since this protective system has been identified in the eye we may assume that vitamin B12 is also involved in protecting ocular tissues.

Laboratory tests in rabbits have shown that local application of vitamin B12 solution more than triples the rate of healing of the cornea.19 There is some evidence to suggest that the eye's normal requirement for vitamin B12 is provided via the tears. This nutrient binds to certain tear proteins to a larger extent than to either proteins in the saliva or gastric juice.20,21

The ability to absorb vitamin B12 is reduced with aging and thus local supplementation may be desirable.22

Direct topical application of vitamin B12 to the eye thus may be useful in replacing locally low levels of the vitamin in tear film deficiency, in eyes stressed by atmospheric conditions, intense and prolonged stare (e.g. computer screen, excessive T.V. viewing), or contact lens wear, and may offer an effective way of ameliorating these conditions and of re-vitalizing the exposed ocular tissues.

[HOSADOS]

Elevated Oncotic Pressure/Complete Wetting

here is a quote from the second lecture.
http://www.dry-eye-institute.org/vitapo.html

Lacrophilic Artificial Tears

There are several commercially available eye drops that are able to wet hydrophobic surfaces, have high oncotic pressure and/or contain nutrients which thus are expected to be efficacious and may be called lacrophilic. We shall briefly discuss these products according to their features.

Elevated Oncotic Pressure/Complete Wetting

The magnitude of the oncotic pressure of various, commercially available, artificial tear substitutes have been directly measured by the means of a Wescor Colloid Osmometer.8 One artificial tear, Hypotears® [IOLAB Pharmaceuticals], appeared to create an initial oncotic pressure high enough to supersede the imbibition pressure of the deturgescent corneal stroma. The authors8 assigned the exceptional patient acceptance and apparent efficacy of HypoTears® to its high oncotic pressure even though the relatively low polymeric content of the formulation should not result such a high oncotic pressure at a thermodynamic equilibrium.

Since then, another artificial tear formulation, formulated for the primary dry eye, has been introduced to the market. Dwelle® [Aqueous Pharma] is an artificial tear that has unique wetting properties and a high enough polymer concentration to create a thermodynamically stable high oncotic pressure (65mmHg). The formulation contains three different polymers. Two polymers form a synergistic mixture that is capable of wetting even an intensely hydrophobic surface. The third polymer is present at a high concentration.

In a double-blind cross-over clinical trial against Tears Naturale® [Alcon Laboratories],4 Dwelle® has healed the ocular surface in twice as many patients as the control drop. In an open clinical trial involving a large number of patients, two-thirds of all patients treated with Dwelle® demonstrated complete healing of the epithelium. The remaining one-third also showed a significant decrease in Rose Bengal staining after two to four weeks of treatment.4 The patients also noticed that they could use the drop less often than other tear substitutes. Despite the high polymeric content, Dwelle® has a relatively low viscosity, about 3 centipoises. However, due to the high polymer (solid) content of the formulation, patients occasionally complain of the stickiness or crusting of the eye lids, especially if their dry eye condition is mild. However, when the ocular surface damage is considerable (Rose bengal staining is above 2+), the use of Dwelle® is justified and the patients will tolerate it well.